VDIProjectSummary/Abstract: The NIH Division of Cell Biology and Biophysics supports studies of the biological macromolecules that affect the function and structure of living cells, and often play a role in disease. Within the realm of biophysics, one of the most important tools to study the structure and interactions of these molecules is nuclear magnetic resonance (NMR). For example, NMR has been used to study the oligomeric forms of amyloid-? that are that are critical to understanding the development of Alzheimer's disease. Also, NMR allows study of the structure of membrane proteins for use as potential pharmaceutical targets. Cleary, NMR is an extremely powerful scientific tool, however, the technique is not simple and the measurements can be expensive and time consuming. This is primarily because the NMR signal is weak and requires sensitive receivers and long integration times for reliable detection. Within the field of NMR, dynamic nuclear polarization (DNP) is a well-known technique to greatly increase the signal strength. Most DNP systems rely on a Gyrotron to generate the required microwave power. Although Gyrotrons generate sufficient power, they are incapable of generating the short pulses and modulated signals desired for advanced DNP systems. Also, their cost is prohibitive for all but the most well-funded laboratories. The key focus of this project is to advance solid-state (SS) source technology to the point where it can begin to replace the Gyrotrons for a significant proportion of DNP-NMR measurements, thereby lowering the barriers to entry into this field and accelerating the pace of scientific discovery. The Phase I effort is focused on demonstrating that recent technological innovations can be used to significantly increase the power and functionality of the SS sources for DNP. The first objective is to demonstrate an innovative frequency doubler design that is expected to generate greater than 200 mW at 263 GHz. This is a significant milestone not only because it will increase the range of measurements possible with a SS source, but also because it is sufficient to fully pump the emerging traveling wave tube (TWT) amplifiers, which can increase the power to the several watts. The second objective is to generate short pulses and complex waveforms with accurate phase and frequency modulation. This is an important milestone because such control of the microwave signal can significantly increase the NMR signal without requiring increased power. The final Phase I objective is to develop the general research plan for Phase II that will lead to watt level power at 263 GHz, extension of the technology to other frequencies of interest, and the implementation of the pulse and modulation controls into a system optimized for DNP- NMR research.